The activation of the renin-angiotensin system (RAS) participates in the development of metabolic syndrome (MetS) and in heart failure. PPAR-alpha activation by fenofibrate reverts some of the effects caused by these pathologies. Recently, nonclassical RAS components have been implicated in the pathogenesis of hypertension and myocardial dysfunction; however, their cardiac functions are still controversial. We evaluated if the nonclassical RAS signaling pathways, directed by angiotensin III and angiotensin-(1-7), are involved in the cardioprotective effect of fenofibrate during ischemia in MetS rats. Control (CT) and MetS rats were divided into the following groups (a) sham, (b) vehicle-treated myocardial infarction (MI-V), and (c) fenofibrate-treated myocardial infarction (MI-F). Angiotensin III and angiotensin IV levels and insulin increased the aminopeptidase (IRAP) expression and decreased the angiotensin-converting enzyme 2 (ACE2) expression in the hearts from MetS rats. Ischemia activated the angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin receptor 1 (AT1R) and angiotensin III/angiotensin IV/angiotensin receptor 4 (AT4R)-IRAP axes. Fenofibrate treatment prevented the damage due to ischemia in MetS rats by favoring the angiotensin-(1-7)/angiotensin receptor 2 (AT2R) axis and inhibiting the angiotensin III/angiotensin IV/AT4R-IRAP signaling pathway. Additionally, fenofibrate downregulated neprilysin expression and increased bradykinin production. These effects of PPAR-alpha activation were accompanied by a reduction in the size of the myocardial infarct and in the activity of serum creatine kinase. Thus, the regulation of the nonclassical axis of RAS forms part of a novel protective effect of fenofibrate in myocardial ischemia.Resistance to apoptosis in chronic myeloid leukemia (CML) is associated with constitutive tyrosine kinase activity of the Bcr-Abl oncoprotein. The deregulated expression of apoptosis-related genes and alteration in epigenetic machinery may also contribute to apoptosis resistance in CML. Tyrosine kinase inhibitors target the Bcr-Abl oncoprotein and are used in CML treatment. The resistance of CML patients to tyrosine kinase inhibitors has guided the search for new compounds that may induce apoptosis in Bcr-Ablleukemic cells and improve the disease treatment.
In the present study, we investigated whether the L-amino acid oxidase isolated from snake venom (BmooLAAO-I) (i) was cytotoxic to Bcr-Ablcell lines (HL-60.Bcr-Abl, K562-S, and K562-R), HL-60 (acute promyelocytic leukemia) cells, the non-tumor cell line HEK-293, and peripheral blood mononuclear cells (PBMC); and (ii) affected epigenetic mechanisms, including DNA methylation and microRNAs expression .
BmooLAAO-I induced ROS production, apoptosis, and differential DNA methylation pattern of regulatory apoptosis genes. The toxin upregulated expression of the pro-apoptotic genes and and downregulated expression in leukemic cell lines, as well as increased miR-16 expression - whose major predicted target is the anti-apoptotic gene - in Bcr-Ablcells.
BmooLAAO-I exerts selective antitumor action mediated by HOrelease and induces apoptosis, and alterations in epigenetic mechanisms. These results support future investigations on the effect of BmooLAAO-I on models to determine its potential in CML therapy.
BmooLAAO-I exerts selective antitumor action mediated by H2O2 release and induces apoptosis, and alterations in epigenetic mechanisms. These results support future investigations on the effect of BmooLAAO-I on in vivo models to determine its potential in CML therapy.This interesting image illustrates an unusual case of inferior vena cava (IVC) syndrome from prostate cancer retroperitoneal adenopathy initially identified with skeletal scintigraphy. IVC syndrome is an infrequent occurrence resulting from extrinsic compression or intraluminal occlusion of the vessel. Whole-body planar skeletal scintigraphy showed a stable left sacroiliac metastasis and increased soft tissue uptake throughout the lower hemibody up to the lower chest level. Computed tomography (CT) demonstrated extrinsic compression of the IVC from metastatic retroperitoneal adenopathy. This represents a rare presentation of IVC syndrome in prostate cancer with characteristic appearance on skeletal scintigraphy of Fisherman's Wader's sign, that should prompt confirmatory anatomic imaging.Prostate-specific membrane antigen (PSMA)-targeted imaging is now an effective tool for the evaluation of prostate cancer patients. Although salivary glands take up 68Ga-PSMA avidly, pathologies of these glands may be readily noticeable. Herein, we present a case of prostate cancer referred for 68Ga-PSMA positron emission tomography-computed tomography in whom an isolated aplasia of the submandibular salivary gland was incidentally found.Osteosarcoma (OS) is a fast-growing tumor, with a high risk of local recurrence and distant metastases, with the lung and bone being the most common sites of dissemination occurring in approximately 80% of cases. Pleural metastases rarely occurs and the appearance of diffuse pleural thickening with ossification is not usual, with few such cases reported due to the current state-of-art treatment protocols. A 29-year-old woman, diagnosed with a proximal left tibial OS underwent planar and single-photon emission computed tomography/computed tomography bone scan scintigraphy with 99mtechnetium methylene diphosphonate showing bilateral pleural uptake, corresponding to multiple calcified foci of thickening and nodules.Primary pancreatic lymphomas are very rare as compared to other pancreatic neoplasms. https://www.selleckchem.com/products/ptc-028.html However, unlike carcinomas, pancreatic lymphoma is treatable with satisfactory cure rates. Somatostatin receptor (SSTR) positron emission tomography/computed tomography (PET/CT) with 68Ga-DOTANOC is a well-established diagnostic modality in the management of neuroendocrine tumors (NETs). Over the years, it has been evident that any neoplasm with SSTR expression shows increased tracer uptake, lymphoma, being the most prominent one. Herein, we report a case of pancreatic mass, suggested as NET on fine-needle aspiration cytology referred to us for staging. Whole-body 68Ga-DOTANOC PET/CT scan showed a large pancreatic mass with peripancreatic nodes, level I cervical nodes, cardiac, and left testicular masses which were initially thought to be possibly metastatic from pancreatic NET. However, immunohistochemistry (IHC) of the specimen was suggestive of B-cell Non-Hodgkin's Lymphoma. The present case emphasizes that pancreatic lymphoma is one of the potential differentials for pancreatic masses apart from NET on SSTR imaging.